A total of 19 randomized controlled trials (RCTs) were eligible for inclusion in this meta-analysis, as they met all four of the following criteria: (1) described as a behavioral intervention; (2) targeted individuals 18 years of age or older; (3) randomly assigned individual participants to intervention and control groups, and; (4) reported outcome data on adherence or VL. All included studies were conducted in high-income countries (United States, Spain, Switzerland, France), with the majority conducted in the United States (74%). Most studies (84%) took place at outpatient HIV primary-care clinics and were conducted with convenience samples.

Search Strategy

Authors searched online trial registry databases and the electronic databases Medline, PubMed, PsycINFO, ERIC, and EMBASE, using relevant keywords for articles published between January 1998 and September 2005. To supplement the search, authors contacted experts in the field, put out a call for relevant studies on a popular HAART research listserv, and reviewed the references of all pertinent articles.

Participants

A total of 1839 male and female adult participants met the selection criteria of the nineteen included randomized controlled trials. Eligibility criteria varied between the included studies, although seven of the 19 studies restricted inclusion to patients exhibiting some marker of risk of non-adherence, such as poor baseline adherence or detectable viral load. Participants in the included studies were mostly male (median 74%). Participants in the United States were mostly racial/ethnic minorities (median 54% African American and 19% Latino Americans).

Intervention(s)

Over half of the interventions included in this meta-analysis were delivered using a one-on-one counseling method; three others used a group format. The most common interveners were healthcare providers such as physicians or nurses (n=9) or mental health counselors such as psychologists (n=5); in 10 of the studies, dedicated research staff, rather than clinical staff, provided the intervention. The median number of intervention sessions was two (range: 1-54 sessions), the median amount of time for each session was 60 minutes (range: 45 minutes to 2.5 hours), and the median intervention duration was 70 days (range: one day to one year). Almost all studies provided didactic information on HAART (79%) or interactive discussions addressing knowledge, motivations, and expectations about taking HAART (79%). Details of the behavioral intervention strategies were reported in 16 of the studies, and five used external reminders (such a pagers, diaries, or calendars).

Outcome Measures

Although the included studies varied in how they defined adherence, in order to reduce the measurement variance the authors of this meta-analysis contacted the authors of the included RCTs and requested data on the percentage of participants who had ≥95% adherence to their regimen, and the percentage of participants with an undetectable HIV-1 VL, based on the assay used in the original research. Of the 19 included studies, 18 assessed ≥95% adherence and 14 assessed undetectable HIV-1 VL. Thirteen of the 19 studies assessed both adherence and undetectable HIV-1 VL. Most (58%) of the studies used self-reports to measure adherence, while the remaining relied on electronic monitoring.

Results

Of the 18 studies that assessed 95% adherence, 62% (484 of 786) of intervention-arm participants and 50% (426 of 847) of control-arm participants achieved 95% adherence. The aggregated effect size was significant (OR=1.50; 95% CI 1.16-1.94) indicating that, overall, the likelihood of achieving at least 95% adherence was higher in the intervention arm than in the control arm. Overall, 62% (379 of 605) of intervention-arm participants and 55% (352 of 642) of control-arm participants achieved an undetectable VL. Four variables were consistently associated with 95% adherence and undetectable VL outcomes. These were studies conducted outside the United States (vs. domestically); studies with interventions that included didactic information on HAART (vs. studies that did not include that information); studies in which the intervention included interactive discussion of knowledge, motivations, and expectations (vs. studies without that feature); and studies in which the outcome data came from the first follow-up (vs. immediate post-intervention assessment).

Conclusions

The authors concluded that various HAART intervention strategies were shown to be successful, but cautioned that more research is needed to identify the most efficacious intervention components and the best methods for implementing them in real-world settings with limited resources.

Quality Rating

Using the QUOROM grading scale for systematic reviews, this study was of high quality, scoring 18 of 18 possible points. Like all meta-analyses, the quality of this study was limited by the limitations of the primary studies; for instance, more than half of the studies relied on self-reported adherence data, which may not provide the most accurate estimates of adherence, and many also did not report potentially important variables (such as specific medication regimens and indicators of resistance). Additionally, because many studies used multiple intervention components, conducting an un-confounded analysis of specific components was not possible.

In Context

The findings of this analysis concur with those of the only other published meta-analysis of HAART adherence intervention studies, in that both analyses found that interventions as a whole were efficacious in improving adherence. However, unlike this analysis, the previous analysis found that the intervention effect was significantly stronger in studies that enrolled only participants with known or anticipated adherence problems, compared with studies that did not target potential participants based on known or anticipated adherence problems.(1)

Programmatic Implications

The findings of this meta-analysis suggest that behaviorally based interventions can have a significant positive effect on self-reported adherence and biological markers of adherence. Note, however, that all these studies were conducted in industrialized countries. In resource-constrained settings, where external factors may differ (such as difficulty in getting to clinics, drug shortfalls, and limited health resources) additional strategies may be needed to achieve high levels of adherence. Nonetheless, studies from Africa (2,3) suggest that substantially higher levels of adherence than in North America and Europe are being achieved. Additional trials are under way in Africa to evaluate setting-appropriate adherence interventions.